Moerlein S M, Dalal K B, Ebbe S N, Yano Y, Budinger T F
Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Int J Rad Appl Instrum B. 1988;15(2):141-9. doi: 10.1016/0883-2897(88)90080-3.
Low-density lipoprotein (LDL) labeled via direct iodination or via the radioiodinated residualizing moiety tyramine-cellobiose (TC) were compared in rabbits as potential 123I radiopharmaceuticals for imaging sites of LDL catabolism. The tissue deposition of 131I-TC-LDL after 24 h as determined by dissection was in the major catabolic organs (liver, adrenals, spleen), and its plasma clearance was slower in rabbits with dietary hypercholesterolemia than in normals. 131I-LDL was unsuitable as a metabolic tracer due to redistribution of catabolites and/or loss of the label before protein degradation, which resulted in little accumulation of radioactivity in catabolic organs and high thyroid uptake. The plasma clearance half-time was similar (ca 22 h) for the two compounds in normal rabbits, but was increased to about 36 h for 131I-TC-LDL and decreased to approximately 9 h for 131I-LDL in hypercholesterolemic animals. The were similar with dynamic imaging of control and hypercholesterolemic rabbits using 123I-labeled analogues. 123I-TC-LDL rapidly localized in the liver, with low thyroid accumulation of radioactivity. The hepatic uptake of 123I-LDL was about half that of 123I-TC-LDL, and thyroid sequestration of radioactivity was significant for 123I-LDL but not 123I-TC-LDL. These data suggest that whereas the residualizing 123I-TC-LDL has a pharmacokinetic profile representative of lipoprotein metabolism, the biodistribution of the activity from injected 123I-LDL is complicated by processes other than protein degradation. The results are discussed with regard to nuclear medicine applications in evaluating lipoprotein catabolism in man.
将通过直接碘化或通过放射性碘化残留部分酪胺 - 纤维二糖（TC）标记的低密度脂蛋白（LDL）作为潜在的用于成像LDL分解代谢部位的123I放射性药物在兔体内进行比较。通过解剖确定，24小时后131I - TC - LDL在主要分解代谢器官（肝脏、肾上腺、脾脏）中的组织沉积情况，并且在饮食性高胆固醇血症的兔中其血浆清除速度比正常兔慢。131I - LDL不适合作为代谢示踪剂，因为分解代谢产物会重新分布和/或在蛋白质降解之前标记物会丢失，这导致在分解代谢器官中几乎没有放射性积累，而甲状腺摄取量高。在正常兔中，两种化合物的血浆清除半衰期相似（约22小时），但在高胆固醇血症动物中，131I - TC - LDL的血浆清除半衰期增加到约36小时，而131I - LDL的血浆清除半衰期降至约9小时。使用123I标记类似物对对照兔和高胆固醇血症兔进行动态成像的结果相似。123I - TC - LDL迅速在肝脏中定位，甲状腺放射性积累较低。123I - LDL的肝脏摄取量约为123I - TC - LDL的一半，并且123I - LDL的放射性在甲状腺中的潴留显著，而123I - TC - LDL则不然。这些数据表明，虽然残留的123I - TC - LDL具有代表脂蛋白代谢的药代动力学特征，但注射的123I - LDL的活性生物分布因蛋白质降解以外的过程而变得复杂。针对核医学在评估人类脂蛋白分解代谢中的应用对结果进行了讨论。
